Site-Specific Effects of Online rTMS during a Working Memory Task in Healthy Older Adults

Abstract

The process of manipulating information within working memory is central to many cognitive functions, but also declines rapidly in old age. Improving this process could markedly enhance the health-span in older adults. The current pre-registered, randomized and placebo-controlled study tested the potential of online repetitive transcranial magnetic stimulation (rTMS) applied at 5 Hz over the left lateral parietal cortex to enhance working memory manipulation in healthy elderly adults. rTMS was applied, while participants performed a delayed-response alphabetization task with two individually titrated levels of difficulty. Coil placement and stimulation amplitude were calculated from fMRI activation maps combined with electric field modeling on an individual-subject basis in order to standardize dosing at the targeted cortical location. Contrary to the a priori hypothesis, active rTMS significantly decreased accuracy relative to sham, and only in the hardest difficulty level. When compared to the results from our previous study, in which rTMS was applied over the left prefrontal cortex, we found equivalent effect sizes but opposite directionality suggesting a site-specific effect of rTMS. These results demonstrate engagement of cortical working memory processing using a novel TMS targeting approach, while also providing prescriptions for future studies seeking to enhance memory through rTMS.

Fast computational optimization of TMS coil placement for individualized electric field targeting

“…Additional MRI-based head models-M1, M2, M3, and M4-were borrowed from one of our experimental studies involving E-field-based dosing [37], corresponding subject ids are S262, S263, S266, and S269. Briefly, the models were constructed using structural T1-weighted To speed-up computation further, we generate auxiliary coil models each modeling a distinct coil orientation.…”

“…For each of the four additional models (M1-M4), four ROIs where generated using the SimNIBS TMS coil placement optimization functionality with diameter of 0.1, 1, 2, and 4 cm (ROI1, ROI2, ROI3, ROI4) derived from fMRI-measured brain activity [37]. The smallest diameter ROIs consist of a single tetrahedron and we defined the diameter for these ROIs as the equivalent sphere diameter 2 (…”

“…Evaluating the TMS induced E-field for a single coil position using a standard resolution head model currently requires 35 seconds using FEM [34] or 104 seconds using a fastmultipole method accelerated BEM [35]. Furthermore, E-field-informed optimal coil placement would require iterative execution of such simulations until an optimal coil position and orientation are found [36,37]. As such, computational requirements limit the routine use of E-field-informed optimization of coil placement.…”

“…As such, computational requirements limit the routine use of E-field-informed optimization of coil placement. For example, for this reason we restricted the individual modelbased dosing in a recent study to selecting only the coil current setting [37]. This paper introduces a computational approach that enables fast E-field-informed optimization of coil placement using high resolution individual head models.…”

“…, across the four subjects, is 1.0 mm. SimNIBS was used to generate coil center positions on 3 cm diameter scalp region centered about the scalp position closest to the ROIs CM[37]. Each coil position was chosen to be approximately 1 mm apart and scalp positions where extruded outward by an amount dependent on the individual hair thicknesse: 3.26, 2.03, 5.55, and 2.78 mm for models M1-M4, respectively[37].…”